SARS-CoV-2-associated gastrointestinal and liver diseases: what is known and what is needed to explore

Abstract Background The pandemic of COVID19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first described in China as an unexplained pneumonia transmitted by respiratory droplets. Gastrointestinal (GI) and liver injury associated with SARS-CoV-2 infection were reported as an early or sole disease manifestation, mainly outside China. The exact mechanism and incidence of GI and liver involvement are not well elucidated. Main body We conducted a PubMed search for all articles written in the English language about SARS-CoV-2 affecting the GI and liver. Following data extraction, 590 articles were selected. In addition to respiratory droplets, SARS-CoV-2 may reach the GI system through the fecal-oral route, saliva, and swallowing of nasopharyngeal fluids, while breastmilk and blood transmission were not implicated. Moreover, GI infection may act as a septic focus for viral persistence and transmission to the liver, appendix, and brain. In addition to the direct viral cytopathic effect, the mechanism of injury is multifactorial and is related to genetic and demographic variations. The most frequently reported GI symptoms are diarrhea, nausea, vomiting, abdominal pain, and bleeding. However, liver infection is generally discovered during laboratory testing or a post-mortem. Radiological imaging is the gold standard in diagnosing COVID-19 patients and contributes to understanding the mechanism of extra-thoracic involvement. Medications should be prescribed with caution, especially in chronic GI and liver patients. Conclusion GI manifestations are common in COVID-19 patients. Special care should be paid for high-risk patients, older males, and those with background liver disease.

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Brexanolone: A Novel Drug for the Treatment of Postpartum Depression

Journal of Pharmacy Practice ◽

10.1177/0897190020979627 ◽

2020 ◽

pp. 089719002097962

Author(s):

Edna Patatanian ◽

David R. Nguyen

Keyword(s):

Adverse Effects ◽

Postpartum Depression ◽

English Language ◽

Neuronal Excitability ◽

Data Extraction ◽

Background Information ◽

Pharmacologic Therapy ◽

Loss Of Consciousness ◽

Efficacy And Safety ◽

Pubmed Search

Objectives: To review the pharmacology, efficacy, and safety of Brexanolone and define its role in the treatment of postpartum depression. Date Sources: A MEDLINE/PubMed search was conducted (1980-May 2020) using the following keywords: postpartum depression, antidepressants, pharmacologic therapy, drug therapy, and brexanolone to identify relevant articles. Study Selection/Data Extraction: Literature search was limited to human studies published in the English language. Phase I, II, and III studies evaluating the pharmacology, efficacy, safety of brexanolone for postpartum depression were included. Bibliographies of relevant articles evaluating postpartum depression and treatment were reviewed for additional citations and background information. Data Synthesis: Brexanolone is a soluble, proprietary, injectable formulation of allopregnanolone, a neuroactive steroid that modulates neuronal excitability. Allopregnanolone levels increase during pregnancy and decrease substantially after birth. These fluctuations have profound effects on anxiety and depression. Three clinical trials established the efficacy and safety of brexanolone in the treatment of postpartum depression. In all 3 trials, brexanolone had an acceptable safety profile and was well tolerated. The most common adverse effects were loss of consciousness, sedation, dry mouth, headache, dizziness, and flushing. Due to sudden loss of consciousness and excessive sedation, continuous pulse oximetry is recommended. Conclusion: Brexanolone has a novel mechanism of action and appears to be safe and effective for the treatment of moderate to severe postpartum depression. At present, high cost, serious adverse effects, and restricted access may limit its use in clinical practice.

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Lead in Mineral or Multivitamin-Multimineral Products

Annals of Pharmacotherapy ◽

10.1177/10600280211023328 ◽

2021 ◽

pp. 106002802110233

Author(s):

C. Michael White

Keyword(s):

English Language ◽

Data Extraction ◽

The United States ◽

Third Party ◽

Reference Level ◽

Study Selection ◽

Pubmed Search ◽

Zinc Supplements ◽

Average Lead ◽

Year 2000

Objective Assess the current daily interim reference level of lead and the amount contained in current mineral and multivitamin-multimineral (MVM) products. Data Sources PubMed search from 1980 to May 15, 2021, limited to the English language, via the search strategy ((mineral OR multivitamin OR calcium OR iron OR magnesium OR copper OR zinc OR chromium OR selenium) AND (heavy metals OR Pb OR lead)). Study Selection and Data Extraction Narrative review of studies assessing lead content in mineral or MVM products. Data Synthesis Products containing different calcium forms (dolomite, bone meal, natural carbonate) have historically had higher lead levels than others (refined carbonate, lactate, gluconate, acetate, sevelamer), but the gap has closed considerably since the year 2000. Although only limited assessments of magnesium and zinc supplements have been conducted, no alarming average lead amounts were found. MVM products assessed since 2007 had low median or mean lead concentrations. However, large interproduct differences exist, with many products having very little lead and some products having concerning amounts. Relevance to Patient Care and Clinical Practice It is difficult for pharmacists and consumers to know the amount of lead in an actual product unless it is tested in an independent third-party lab. The United States Pharmacopeia and NSF International will provide a seal on the products stating that the products have a low level of lead, but even so, children could receive more lead than the Food and Drug Administration’s Interim Reference Level. Conclusions The threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid.

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Esketamine: A Novel Option for Treatment-Resistant Depression

Annals of Pharmacotherapy ◽

10.1177/1060028019892644 ◽

2019 ◽

Vol 54 (6) ◽

pp. 567-576 ◽

Cited By ~ 1

Author(s):

Kevin M. Bozymski ◽

Ericka L. Crouse ◽

Erika N. Titus-Lay ◽

Carol A. Ott ◽

Jill L. Nofziger ◽

...

Keyword(s):

English Language ◽

Rating Scale ◽

Data Extraction ◽

Fixed Dose ◽

Depression Symptoms ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Pubmed Search ◽

Resistant Depression ◽

Suicidal Thoughts And Behaviors

Objective:To review the pharmacology, pharmacokinetics, efficacy, safety, use requirements, and place in therapy of esketamine for treatment-resistant depression (TRD). Data Sources: A comprehensive PubMed search (1966 to October 2019) was conducted using the search terms depression, treatment-resistant, suicide, intranasal, esketamine, and JNJ-54135419. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling, and Clinicaltrials.gov . Study Selection and Data Extraction: All English-language trials evaluating intranasal esketamine for TRD were included and discussed. Data Synthesis: Intranasal esketamine was approved by the US Food and Drug Administration, in conjunction with an oral antidepressant, for treating TRD in adults. Two short-term trials (TRANSFORM-1 and -2) found statistically significant reduction in the Montgomery-Asberg Depression Rating Scale score at day 28 for the fixed 56-mg dose (−4.1; 95% CI = −7.69 to −0.49; P = 0.027 [exploratory]) and flexible-dosed arms (−4.0; 95% CI = −7.31 to −0.64; P = 0.02), though the fixed-dose 84-mg arm (−3.2; 95% CI = −6.88 to 0.45; P = 0.088) of TRANSFORM-1 and TRANSFORM-3 did not (−3.6; 95% CI = −7.2 to 0.07; P = 0.059). Two long-term trials (SUSTAIN-1 and -2) suggested maintenance of response with continued use. Esketamine’s adverse effects include dizziness, dysgeusia, somnolence, dissociation, suicidal thoughts and behaviors, and increased heart rate and blood pressure. Relevance to Patient Care and Clinical Practice: Although providing a novel antidepressant mechanism and formulation for TRD, esketamine’s role in treatment will likely be limited by cost, administration, and diversion concerns. Conclusion: Intranasal esketamine significantly reduced depression symptoms in TRD, though with tolerability issues.

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Can Orthopaedics become the Gold Standard for Reproducibility? A Roadmap to Success

10.1101/715144 ◽

2019 ◽

Author(s):

Ian A. Fladie ◽

Sheridan Evans ◽

Jake Checketts ◽

Daniel Tritz ◽

Brent Norris ◽

...

Keyword(s):

Empirical Data ◽

Orthopaedic Surgery ◽

English Language ◽

Data Extraction ◽

Data Availability ◽

Data Sets ◽

Level Of Evidence ◽

Pubmed Search ◽

Peer Reviewers ◽

Research Findings

AbstractBackgroundScientific research is replete with poor accessibility to data, materials, and protocol, which limits the reproducibility of a study. Transparency with regard to materials, protocols, and raw data sets enhances reproducibility by providing the critical information necessary to verify, replicate, and resynthesize research findings. The extent to which transparency and reproducibility exist in the field of orthopaedics is unclear. In our study, we aimed to evaluate transparency and reproducibility-related characteristics of randomly sampled publications in orthopaedic journals.MethodsWe used the National Library of Medicine catalog to identify English language and MEDLINE-indexed orthopaedic journals. From the 74 journals meeting our inclusion criteria, we randomly sampled 300 publications using a refined PubMed search that were published between January 1, 2014, and December 31, 2018. Two investigators were trained for data extraction and analysis. Both investigators were blinded and independently extracted data from the 300 studies.ResultsOur initial search yielded 68,102 publications, from which we drew a random sample of 300 publications. Of these 300 publications, 286 were screened for empirical data and 14 were inaccessible. For analysis purposes, we excluded publications without empirical data. Of the 182 with empirical data, 13 studies (7.1%) included a data availability statement, 9 (4.9%) reported materials were available, none (0.0%) provided analysis scripts, 2 (1.1%) provided access to the protocol used, 5 (2.7%) were preregistered, and only 2 (1.1%) provided a statement about being a replicated study.ConclusionsComponents necessary for reproducibility are lacking in orthopaedic surgery journals. The vast majority of publications did not provide data or material availability statements, protocols, or analysis scripts, and had no preregistration statements. Intervention is needed to improve reproducibility in the field of orthopaedics. The current state of reproducibility in orthopaedic surgery could be improved by combined efforts from funding agencies, authors, peer reviewers, and journals alike.Level of EvidenceN/A

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Delafloxacin for the Treatment of Acute Bacterial Skin and Skin Structure Infections

Journal of Pharmacy Technology ◽

10.1177/8755122519834615 ◽

2019 ◽

Vol 35 (3) ◽

pp. 110-118

Author(s):

Young Ran Lee ◽

Caitlin Elizabeth Burton ◽

Kolton Rucks Bevel

Keyword(s):

Treatment Option ◽

English Language ◽

Data Extraction ◽

Additional Treatment ◽

Effective Treatment Option ◽

Skin Structure ◽

Patient Morbidity ◽

Study Selection ◽

Pubmed Search

Objective: To review the microbiological activity, safety, and efficacy of the new fluoroquinolone delafloxacin for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Data Sources: A PubMed search from 1945 to September 2018 was done using the terms delafloxacin, acute bacterial skin and skin structure infections, skin and soft tissue infections, and fluoroquinolone. Additional sources include the Food and Drug Administration website, ClinicalTrials.gov, and the Melinta Therapeutics website. Study Selection and Data Extraction: The literature search was limited to those published in the English language and included in vitro and human studies that evaluated microbiological coverage, pharmacokinetics, pharmacodynamics, safety, and/or efficacy. Data Synthesis: Delafloxacin is a new fluoroquinolone with a unique structure for its class that covers both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. This new antibiotic has demonstrated noninferiority to vancomycin plus aztreonam for the treatment of ABSSSIs in both an intravenous-only regimen and an intravenous to an oral regimen. Relevance to Patient Care and Clinical Practice: ABSSSIs are infections that are most often caused by Staphylococcus and represent one of the most common types of hospital infections. MRSA represents about half of all staphylococcal skin infections, and along with gram-negative infections, increase the rates of patient morbidity and health care costs. Delafloxacin is an additional treatment option that covers both of these types of microorganisms. Conclusions: Delafloxacin is a safe and effective treatment option for ABSSSIs, particularly in those with polymicrobial infections and those with MRSA.

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Sufentanil Sublingual Tablet: A New Option for Acute Pain Management

Annals of Pharmacotherapy ◽

10.1177/1060028019863144 ◽

2019 ◽

Vol 53 (12) ◽

pp. 1220-1226 ◽

Cited By ~ 3

Author(s):

Caitlin E. Reardon ◽

Sandra L. Kane-Gill ◽

Pamela L. Smithburger ◽

Joseph F. Dasta

Keyword(s):

Acute Pain ◽

English Language ◽

Data Extraction ◽

Unmet Need ◽

Phase Iii ◽

Pain Intensity Score ◽

Sublingual Tablet ◽

Phase Iii Clinical Trials ◽

Study Selection ◽

Pubmed Search

Objective: The purpose of this article is to review the safety and efficacy of sufentanil sublingual tablet (SST) and suggest its place in therapy for managing acute pain in patients requiring intravenous (IV) opioids. Data Sources: A MEDLINE/PubMed search was performed (2010 to April 2019) using the following keywords: sufentanil sublingual tablet, sufentanil, opioid, moderate to severe acute pain. Study Selection and Data Extraction Quantification: We included English language articles evaluating SST pharmacology, pharmacokinetics, efficacy, and safety in humans for the treatment of acute pain. Data Synthesis: SST is Food and Drug Administration approved and considered safe and effective for the treatment of acute pain in Risk Evaluation and Mitigation Strategy–certified and medically supervised health care settings. Phase III clinical trials showed a statistically significant decrease in summed pain intensity score when SST was compared with placebo. Relevance to Patient Care and Clinical Practice: SST can be a useful option in patients requiring a parenteral opioid who do not have IV access, or it may be unnecessary or difficult to obtain. Because of its quick onset and sustained analgesia, SST may also be useful for procedural pain in the critically ill, to expedite discharges for outpatient procedures, in emergency departments (EDs), and in the battlefield. Conclusions: SST can satisfy an unmet need in patients with acute pain, who require parenteral opioids, and either have no IV access or require prolonged time to achieve IV access such as patients in outpatient surgical centers, EDs, and the battlefield. During periods of parenteral opioid shortage, SST may provide another option for adequate analgesia.

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Evaluating Reproducibility and Transparency in Emergency Medicine Publications (Preprint)

10.2196/preprints.15639 ◽

2019 ◽

Author(s):

Bradley Johnson ◽

Shelby Rauh ◽

Daniel Tritz ◽

Michael Schiesel ◽

Ben Matthew Vassar

Keyword(s):

Emergency Medicine ◽

Data Analysis ◽

English Language ◽

Data Extraction ◽

Inclusion Criteria ◽

Raw Data ◽

Medicine Research ◽

Funding Agencies ◽

Pubmed Search ◽

Peer Reviewers

BACKGROUND Reproducibility is the backbone to ensuring reliable and transparent research. However, evidence reveals reproducibility may be lacking within emergency medicine. Reproducibility is defined by the replication of a study design and obtaining similar findings. Studies that share research components such as raw data, protocols, and analysis scripts increase the overall reproducibility by aiding study replication. Due to the evidence reproducibility in emergency medicine research may be lacking, investigation of the sharing of these research components is warranted. OBJECTIVE We aimed to assess the reproducibility of empirical research by determining the availability of components required for replication of a study, including materials, raw data, analysis scripts, protocols, and preregistration. METHODS The National Library of Medicine catalog was used to identify English language and MEDLINE-indexed emergency medicine journals. From 30 journals that met the inclusion criteria, 300 publications from January 1, 2014, to December 31, 2018, were randomly sampled using a refined PubMed search. Two investigators were trained for data extraction and analysis and were blinded for independent extraction of data. Extracted data included statements regarding the availability of materials, data, analysis scripts, protocols, and registration. RESULTS After search criteria were set, 25,473 articles were found, from which we randomly selected a sample of 300. Of the 300 articles, only 290 articles were accessible, and of these, 178 articles contained empirical data to analyze. Of the empirical articles eligible for each type of statement, 3.94% (95% confidence interval [95% CI] 1.74% to 6.14%) provided a materials statement, 9.42% (95% CI 6.11% to 12.73%) provided a data statement, 0.72% (95% CI 0% to 1.68%) provided access to the analysis scripts, 2.17% (95% CI 0.52% to 3.82%) linked the protocol, and 7.25% (95% CI 4.31% to 10.18%) were preregistered. CONCLUSIONS Emergency medicine studies are lacking indicators required for reproducibility. The vast majority of studies fail to report factors needed to reproduce research to ensure credibility, which requires an intervention that can be achieved through the collaboration of researchers, peer reviewers, funding agencies, and journals.

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Pharmacy Technicians and Improving Onychomycosis Treatment Outcomes

Journal of Pharmacy Technology ◽

10.1177/8755122518815057 ◽

2018 ◽

Vol 35 (2) ◽

pp. 82-87

Author(s):

Sherrill J. Brown

Keyword(s):

Treatment Outcomes ◽

Treatment Adherence ◽

English Language ◽

Positive Impact ◽

Data Extraction ◽

Improve Treatment ◽

Treatment And Prevention ◽

Pubmed Search ◽

Pharmacy Technicians ◽

The Impact

Objective: To provide an overview of onychomycosis and current treatments and to identify opportunities for pharmacy technicians to improve treatment outcomes. Data Sources: A MEDLINE/PubMed search (1966 to October 2018) was performed using search terms designed to identify English-language articles on onychomycosis diagnosis, treatment, and prevention, as well as articles on the impact of pharmacy technicians on onychomycosis outcomes and the use of pharmacy technicians to improve treatment adherence. Study Selection and Data Extraction: Review articles and clinical studies describing onychomycosis, risk factors, treatment efficacy, and prevention of recurrent infections were included. Data Synthesis: Although no articles on the impact of pharmacy technicians in the treatment of onychomycosis were found, the importance of treatment adherence on positive outcomes highlights a potential role of pharmacy technicians. Pharmacy technicians can identify patients with potential onychomycosis based on questions about over-the-counter products and refer patients to the pharmacist for counseling on treatment. Pharmacy technicians can also reinforce treatment adherence at refill visits. Conclusions: Pharmacy technicians can have a positive impact on onychomycosis treatment outcomes by addressing barriers to successful treatment and promoting treatment adherence.

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Eravacycline: The Tetracyclines Strike Back

Annals of Pharmacotherapy ◽

10.1177/1060028019850173 ◽

2019 ◽

Vol 53 (11) ◽

pp. 1124-1135 ◽

Cited By ~ 10

Author(s):

Maria Heaney ◽

Monica V. Mahoney ◽

Jason C. Gallagher

Keyword(s):

English Language ◽

Adverse Drug Events ◽

Data Extraction ◽

Multidrug Resistant ◽

Phase Iii ◽

Language Studies ◽

Mesh Terms ◽

Multidrug Resistant Organisms ◽

Pubmed Search

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of eravacycline, a novel fluorocycline antibiotic from the tetracycline family. Data Sources: A PubMed search was conducted for data between 1946 and March 2019 using MeSH terms eravacycline and TP-434. An internet search was conducted for unpublished clinical research. Study Selection and Data Extraction: The literature search was limited to English-language studies that described clinical efficacy, safety, and pharmacokinetics in humans and animals. Abstracts featuring prepublished data were also evaluated for inclusion. Data Synthesis: Eravacycline has in vitro activity against multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, extended-spectrum β-lactamase-producing and carbapenem-resistant Enterobacteriaceae, and Acinetobacter. It was approved for the treatment of complicated intra-abdominal infections (cIAIs) in adults following favorable results of 2 phase III trials, IGNITE 1 and IGNITE 4, compared with ertapenem and meropenem, respectively. The most common adverse drug events associated with eravacycline were infusion site reactions (7.7%), nausea (6.5%), vomiting (3.7%), and diarrhea (2.3%). Relevance to Patient Care and Clinical Practice: Eravacycline will likely be most useful for resistant infections when lack of tolerability, resistant phenotypes, or allergies prevent the use of β-lactams. Conclusions: Eravacycline is a new tetracycline antibiotic with a broad spectrum of activity that has demonstrated efficacy in the treatment of cIAIs. Although it has activity against multidrug-resistant organisms, data are limited for other indications.

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Use of real-time videoconferencing to deliver physical therapy services: A scoping review of published and emerging evidence

Journal of Telemedicine and Telecare ◽

10.1177/1357633x19854647 ◽

2019 ◽

Vol 26 (10) ◽

pp. 581-589 ◽

Cited By ~ 1

Author(s):

Stephanie Horsley ◽

Gunnar Schock ◽

Stacey L Grona ◽

Kara Montieth ◽

Bryttnee Mowat ◽

...

Keyword(s):

Physical Therapy ◽

Real Time ◽

English Language ◽

Data Extraction ◽

Therapy Assessment ◽

Process Outcomes ◽

Study Characteristics ◽

Therapy Services ◽

Videoconferencing Technology ◽

Physical Therapy Services

Introduction Telehealth may be a viable means to deliver physical therapy services across a range of practice settings and health conditions; however, there is limited uptake of telehealth in clinical practice. The purpose of this study is to examine and describe trends, gaps and opportunities in published and emerging evidence regarding the use of real-time videoconferencing to deliver physical therapy services. Methods Four databases and three trial registries were searched using terms for physical therapy and telehealth. Inclusion criteria were primary studies, systematic reviews and published trial registries that had the following features: physical therapy assessment and/or treatment, real-time videoconferencing and English language. Title/abstract, full text screening and data extraction were completed by pairs of independent reviewers. Descriptive statistics stratified by published research and trial registry records were used to summarize study characteristics. Results A total of 100 studies (80 published and 20 trial registries) were included. Australia, Canada and the US have the highest proportion of published and emerging research (63%). The majority of conditions studied were musculoskeletal (42%). Computers were the most common videoconferencing technology used (31%) and only 14% of studies reported using a secure platform. The majority of studies examined health outcomes (64%) and process outcomes (65%), while only 32% reported system outcomes. Discussion Research in the field of telehealth and physical therapy is growing and becoming increasingly diverse with the advancements in technology.

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